Resatorvid (TAK-242) is a selective Toll-like receptor 4 (TLR4) inhibitor. Resatorvid inhibits NO, TNF-R and IL-6 production with IC_50s of 1.8 nM, 1.9 nM and 1.3 nM, respectively. Resatorvid downregulates expression of TLR4 downstream signaling molecules MyD88 and TRIF. Resatorvid inhibits autophagy and plays pivotal role in various inflammatory diseases^[1][2]. IC50 & Target: TLR4^[1] In Vitro: Resatorvid suppresses the production of NO, TNF-α, and IL-6 from LPS-stimulated human peripheral blood mononuclear cells (PBMCs) at IC₅₀ values from 11 to 33 nM^[1].
Resatorvid (1-100 nM; 4 hours) inhibits mRNA expression of IL-6 and TNF-α induced by LPS and IFN-γ in RAW264.7 cells^[1].
Resatorvid (1-100 nM; 15 minutes; PBMCs cells) markedly inhibits the LPS-induced phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2), p38, and JNK/SAPK as well as degradation of IκBβ at a concentration of 100 nM^[1]. In Vivo: Resatorvid (0.3 mg/kg; intraperitoneal injection; twice a week; for 4 weeks; ApoE knockout and wild-type mice) treatment inhibites serum autoantibodies (ANA and anti-dsDNA), cytokines (IFN-γ, TNF-α, IL-1β), lung inflammation, and intima-media thickness in brachiocephalic artery^[3].